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Children are at risk of flu complications and can spread the virus to vulnerable populations like the elderly, so they are an important target for annual vaccination. However, a recent study1 found some parents do not seek vaccination for their children based on the perception that it is not needed or their kids don’t get the flu.

That is a troubling sign, given that children can be hospitalized and even die after acquiring influenza. And it is not particularly surprising that some parents may say their kids skip the seasonal flu vaccine because they never get the flu. Flu vaccine and immunizations in general are subject to a host of myths and false assumptions. However, the problem with this one — particularly in terms of the overall goal of universal vaccination — is that at some level it might be true.

Evidence of “genetically determined innate resistance” to rotavirus has been found, suggesting a gene variation in some people is more protective than the rotavirus vaccine.

“[In previous rotavirus research], the gene variations were more protective than the vaccines themselves,” says study author Scott Field, MD, a pediatrician and flu researcher at the University of Alabama School of Medicine in Tuscaloosa. “This isn’t immunity like we think of from getting a vaccine or having an infection. This is an inability, a resistance in the body to uptake of virus. They do not have the [cellular] receptors that are needed to get infected by the virus. The people who didn’t have [the genetic variation] were more susceptible to rotavirus and are needed to get the vaccine.”

Field raises a fascinating point in the paper, asking, “could some parents be right in saying that their child’s risk of getting inﬂuenza without the vaccination is low? … Natural or innate inﬂuenza resistance has biologic plausibility and could explain this study’s ﬁnding of previous inﬂuenza as a potentially important modiﬁer of vaccine efficacy and disease risk.”

A Key Marker

In looking at flu specifically, the researcher found that one genetic variation more often found in African-Americans lowers expression of a protein that is a key marker in people hospitalized with flu infection.

“[The protein] is rare in Sub-Saharan African populations, which may relate to the lower vaccination rates among black patients because of their perceived and possibly true lower risks,” the author reports. “This could partially explain the discrepancy in the literature and in this study between inﬂuenza vaccination rates in blacks versus whites.”

While a compelling scientific point, getting into this level of minutia has the potential to confound the critical public health message to immunize everyone six months and older with the flu vaccine, which is safe and generally effective year to year.

“At this point, I think it still needs to be recommended universally,” Field says. “There may come a day you can do a gene test on everybody and say these people need [flu shots] as these people don’t. I don’t think we are at that point right now.”

The study also found that having had inﬂuenza before may increase a child’s risk signiﬁcantly for being infected again in the absence of vaccination. This seems counterintuitive to some degree, as one might assume prior infection may provide some level of immunity and less severe future infection.

“The increased risk there would be that people who have had flu have the right kind of receptors to get flu,” Field says. “There are [several] strains of flu — in fact, some people get more than one strain in the same season. They get an A strain early in the season and are infected with flu again the second time with B strains. So even though you get immunity from having the disease, that is only for that strain. You can still get flu from a different strain, and you would be more likely to get flu again later with a different strain than someone who can never get the flu.”

The study used an attitudinal survey and medical records from 131 patients in a pediatric practice who were tested for inﬂuenza in the 2012-2013 season. Medical records plus questionnaires determined vaccine, disease history, and attitudes toward flu vaccine. Inﬂuenza-negative and positive cases were closely matched to control groups. The study shed light on the infrequency with which many families experience influenza firsthand. Most positive patients had no history of infection, but those that had been infected had significantly more risk of acquiring flu again, Field notes.

“These are not all absolutes — they are probably all relative things,” he says. “Some may be at low risk, but they are not at no risk.”

Perfect Storm

In another flu vaccine study2 that has raised some questions and concerns, Canadian researchers report that under certain conditions, a history of immunization increases the likelihood of flu infection. The study is a potentially important, but not necessarily welcome, finding as the never-ending struggle to immunize the population against seasonal influenza continues.

The lead author could not be reached for comment as this issue went to press, but the paper describes a “perfect storm” of factors behind the finding that people who were immunized every year since 2012–2013 were at a 54% higher risk of contracting influenza A(H3N2) infection than those consistently unvaccinated. The effect was proceeded by antigenically drifted virus and successive seasons of identical, but mismatched, vaccine.

A vaccine expert was asked about the findings at a recent press conference on influenza at the National Foundation for Infectious Diseases in Washington, DC.

“Our Canadian colleagues who have published that [found] with repeated seasonal vaccination, it looked like there was a statistically significant decrease in the vaccine efficacy compared to those who are not vaccinated every season,” said Wilbur Chen, MD, of the University of Maryland School of Medicine’s Center for Vaccine Development. “This has not been replicated, as I understand, by the CDC in the U.S. So this is an observation that has been seen. We don’t know what to think about it. It is statistically significant, but I don’t think that it detracts away from our message that everyone should get vaccinated. I think it’s a very interesting scientific question and people are exploring it. I’m not sure if there’s a biological mechanism that we’ve been able to [detect] that solidly explains this phenomenon. And again, it hasn’t been replicated at this point.”